Changes of stem cell niche during experimental pituitary tumor development

• Published in: Journal of neuroendocrinology 2021-12, Vol.33 (12), p.e13051-n/a
• Main Authors: Guido, Carolina Beatriz, Sosa, Liliana del Valle, Perez, Pablo Aníbal, Zlocoswki, Natacha, Velazquez, Fabiola Noelia, Gutierrez, Silvina, Petiti, Juan Pablo, Mukdsi, Jorge Humberto, Torres, Alicia Inés
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Brain cancer; Brain tumors; CD44 antigen; Localization; Nestin; pituispheres; Pituitary; Pituitary gland; pituitary stem cell; pituitary tumor; SC markers; Sox9 protein; Stem cells; Tumors
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/jne.13051

To investigate the putative stem cell/tumor stem cell (SC/TSC) niche contribution to hyperplasic/adenomatous pituitary lesions, we analyzed variation in the pituitary stem cell population during the development of experimental pituitary tumors. Pituitary tumors were induced in female F344 rats with estradiol benzoate for 5, 10, 20 and 30 days. Cells positive for GFRa2, Sox2, Sox9, Nestin, CD133 and CD44 were identified in the marginal zone and in the adenoparenchyma in both control and 30D groups, with predominant adenoparenchyma localization of GRFa2 and SOX9 found in tumoral pituitaries. GFRa2, Nestin, CD133 and CD44 were upregulated at the initial stages of tumor growth, whereas Sox9 significantly decreased at 5D, with Sox2 remaining invariable during the hyperplasic/adenomatous development. In addition, isolated pituispheres from normal and tumoral pituitary glands enriched in SC/TSC were characterized. Pituispheres from the 30D glands were positive for the above‐mentioned markers and showed a significant increase in the proliferation. In conclusion, our data revealed pituitary SC pool fluctuations during hyperplastic/adenomatous development, with differential localization of the SC/TSC niche in this process. These findings may help to provide a better understanding of these cell populations, which is crucial for achieving advancements in the field of pituitary tumor biology. The pituitary stem cell population had diverse states of stemness with respect to experimental tumor pituitary development. The stem cells present fluctuations and changes in their distribution of the marginal zone and adenoparenchyma during tumor pituitary development. The pituispheres isolated from the tumoral gland have a multipotent capacity and high proliferative activity.